Retrospective Analysis of Pediatric and Adult Populations Using an LC-MS/MS Method for Oxcarbazepine/Eslicarbazepine Metabolite

Abstract

Abstract Background Therapeutic drug monitoring of anti-epileptic drugs is important to manage seizure control in patients with epilepsy. Oxcarbazepine is a second-generation anti-epileptic drug approved for use in pediatric patients, and eslicarbazepine acetate is a newer generation drug used as adjunctive therapy and monotherapy for partial-onset (focal) seizures. While several second and third generation anti-epileptic drugs have broader therapeutic efficacy in patients, these drugs can still have severe side effects and variable interpatient pharmacokinetics. Consequently, there is a need for accurate and sensitive analytical methods to support therapeutic drug monitoring. Methods An assay improvement for a LC-MS/MS method was developed for the major metabolite of oxcarbazepine and eslicarbazepine, licarbazepine (MHD), using a 13C-labeled form of the compound as the internal standard. Additionally, retrospective data analysis was used to compare the distribution of results observed in adult vs pediatric patients. Results Accuracy and linearity across the analytical measuring range of 1 to 60 µg/mL was acceptable. Inter- and intra-run precision was less than 6% at 3 concentrations tested. The limit of detection was determined to be 0.5 µg/mL. Significant interference from hemolysis, icterus, lipemia, or 187 other potential interferences was not detected. Conclusions The improved assay for MHD was appropriate for clinical use. Retrospective data analysis showed that pediatric and adult patients had a similar distribution of oxcarbazepine/eslicarbazepine metabolite concentrations in serum.